Researchers suggest better ways to test migraine drugs in adolescent populations

April 1, 2013 – P. Brian Smith, MD, was one of the researchers who reviewed pediatric migraine trials to identify possible reasons for the low success rate.

Migraines can occur in up to 20 percent of adolescents and can contribute to a significant number of absences from school for these students. The U.S. Food and Drug Administration (FDA) has only approved two drugs for treating migraines in the pediatric population, despite numerous pediatric trials that have tested the safety and effectiveness of other migraine drugs (triptans). Researchers recently completed a systematic review of pediatric migraine trials to identify possible reasons why most triptan drugs are not effective treatments in adolescents.

The results of the review were published in the March issue of the Journal of the American Medical Association Pediatrics. The DCRI’s P. Brian Smith, MD, was one of the authors.

Many medications, which are safe and effective in adults, have substantial differences in safety, effectiveness, and dosing in a pediatric population. Although pediatric trials have resulted in more than 400 labeling changes for drugs when used with pediatric patients, many of these label updates did not include safety or effectiveness data.

For the systematic review, researchers analyzed pediatric studies for five different migraine drugs that have been proven to be effective treating adult migraines. Each drug had at least one pharmacokinetic (PK) and one efficacy trial submitted to the FDA between 1999 and 2011. For the PK trials, researchers also compared dosing, absorption rates, and bioavailability between pediatric and adult patients for the same drug. Until 2008, only one drug out of the five, almotriptan, was found to be effective in adolescents. In 2011, a second pediatric trial for rizatriptan was submitted to the FDA and demonstrated effectiveness.

One of the challenges with testing triptans to treat adolescent migraines is a high response rate in the groups randomly assigned to receive a placebo instead of a trial drug. Researchers for this review confirmed the high response rate in the placebo groups, which was likely a significant reason most of the trials did not demonstrate effectiveness. Researchers theorized that children might need additional education about the concept of placebos before enrolling in a trial, as well as the reassurance that it is acceptable to report that a treatment didn’t work.

For future studies of migraine drugs, the review team suggested the use of innovative trial designs intended to reduce the placebo response rate. One possible method is to initially treat all patients with a placebo during their first migraine attack, prior to randomization. For example, all patients would initially receive a placebo, and those patients who responded within 30 minutes would be excluded from the trial. The second rizatriptan trial used this approach and was able to demonstrate effectiveness of the trial drug. This approach was not used in the first rizatriptan trial.

Migraines among adolescents may also not be the same type of migraines as seen in adults. The researchers recommend conducting pathophysiological studies of migraines in adolescents to better understand any similarities and differences between migraines in adults. For example, migraines that resolve faster among adolescents might actually be a different type of migraine and those patients may not benefit from migraine drugs.